全文获取类型
收费全文 | 37995篇 |
免费 | 3013篇 |
国内免费 | 1825篇 |
专业分类
耳鼻咽喉 | 460篇 |
儿科学 | 1081篇 |
妇产科学 | 621篇 |
基础医学 | 8532篇 |
口腔科学 | 502篇 |
临床医学 | 2900篇 |
内科学 | 6786篇 |
皮肤病学 | 705篇 |
神经病学 | 2240篇 |
特种医学 | 647篇 |
外国民族医学 | 6篇 |
外科学 | 3242篇 |
综合类 | 5417篇 |
现状与发展 | 6篇 |
预防医学 | 1740篇 |
眼科学 | 653篇 |
药学 | 2235篇 |
3篇 | |
中国医学 | 339篇 |
肿瘤学 | 4718篇 |
出版年
2024年 | 40篇 |
2023年 | 324篇 |
2022年 | 631篇 |
2021年 | 1002篇 |
2020年 | 953篇 |
2019年 | 859篇 |
2018年 | 852篇 |
2017年 | 989篇 |
2016年 | 1083篇 |
2015年 | 1203篇 |
2014年 | 1892篇 |
2013年 | 2179篇 |
2012年 | 2055篇 |
2011年 | 2370篇 |
2010年 | 2022篇 |
2009年 | 2134篇 |
2008年 | 2421篇 |
2007年 | 2513篇 |
2006年 | 2526篇 |
2005年 | 2426篇 |
2004年 | 2000篇 |
2003年 | 1873篇 |
2002年 | 1510篇 |
2001年 | 1364篇 |
2000年 | 1109篇 |
1999年 | 1006篇 |
1998年 | 809篇 |
1997年 | 693篇 |
1996年 | 433篇 |
1995年 | 418篇 |
1994年 | 284篇 |
1993年 | 198篇 |
1992年 | 119篇 |
1991年 | 114篇 |
1990年 | 78篇 |
1989年 | 67篇 |
1988年 | 62篇 |
1987年 | 32篇 |
1986年 | 31篇 |
1985年 | 33篇 |
1984年 | 19篇 |
1983年 | 11篇 |
1982年 | 24篇 |
1981年 | 19篇 |
1980年 | 18篇 |
1979年 | 8篇 |
1978年 | 3篇 |
1977年 | 7篇 |
1976年 | 3篇 |
1970年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 27 毫秒
21.
Alex Jaimes Rosa Guerrero‐Lpez Beatriz Gonzlez‐Girldez Jose M. Serratosa 《Epileptic Disord》2020,22(3):323-326
SCN1A is one of the most relevant epilepsy genes. In general, de novo severe mutations, such as truncating mutations, lead to a classic form of Dravet syndrome (DS), while missense mutations are associated with both DS and milder phenotypes within the GEFS+ spectrum, however, these phenotype‐genotype correlations are not entirely consistent. Case report. We report an 18‐year‐old woman with a history of recurrent febrile generalized tonic‐clonic seizures (GTCS) starting at age four months and afebrile asymmetric GTCS and episodes of arrest, suggestive of focal impaired awareness seizures, starting at nine months. Her psychomotor development was normal. Sequencing of SCN1A revealed a heterozygous de novo truncating mutation (c.5734C>T, p.Arg1912X) in exon 26. Conclusion. Truncating mutations in SCN1A may be associated with milder phenotypes within the GEFS+ spectrum. Accordingly, SCN1A gene testing should be performed as part of the assessment for sporadic patients with mild phenotypes that fit within the GEFS+ spectrum, since the finding of a mutation has diagnostic, therapeutic and genetic counselling implications. 相似文献
22.
23.
Analysis of Heterozygous BRCA1 5382ins Founder Mutation in a Cohort of Egyptian Breast Cancer Female Patients Using Pyrosequencing Technique 下载免费PDF全文
Salwa H Gomaa MogahedYasser S HamedYassmin E Ibrahim MoursyMarwa H Mahomoud Saied 《Asian Pacific journal of cancer prevention》2020,21(2):431-438
Background: Up to half of the heritable mutations in breast cancer (BC) are attributed to BRCA1 and BRCA2 genes. The mutation prevalence is variable based on ethnicity and may be influenced by founder mutations. The aim of this pilot study is to determine for the first time, the prevalence of BRCA1 5382insC founder mutation in a cohort of Egyptian familial breast cancer patients (FBC). Methods: Female patients were selected to have familial type of breast cancer. Twenty healthy females were included as a control group. Peripheral blood samples were withdrawn from all studied females and were analyzed for BRCA1 5382insC founder mutation detection using pyrosequencing technique. Results: Eighty Egyptian FBC females were eligible to be enrolled in the study with a mean age of 48.31 ± 10.97years.We found a BRCA1 5382insC mutation carrier frequency of 5% of total studied FBC patients (4 out of 80 patients) with 95% confidence interval (1.61-12.99). There was a high statistical significant difference between carriers and non-carriers concerning the number of affected family members by BC, (p=0.001). Conclusion: BRCA1 5382insC founder mutation is not uncommon among Egyptian FBC females. The carrier frequency is comparable to that reported worldwide; however it is lower than those from previous Egyptian studies using different molecular techniques. The strong association between the mutation and the number of affected family members suggest wider screening of the mutation among high risk families using the reliable pyrosequencing technique. 相似文献
24.
The main of this study was to evaluate the mutagenic and carcinogenic potential of (+) – usnic acid (UA), using Somatic Mutation and Recombination Test (SMART) and the test for detecting epithelial tumor clones (wts) in Drosophila melanogaster. Larvae from 72 ± 4 h from Drosophila were fed with UA (5.0, 10.0 or 20.0 mM); urethane (10.0 mM) (positive control); and solvent (Milli-Q water, 1% Tween-80 and 3% ethanol) (negative control). ST cross produced increase in total mutant spots in the individuals treated with 5.0, 10.0 or 20.0 mM of UA. HB cross produced spot frequencies in the concentration of 5.0 mM that were higher than the frequency for the same concentration in the ST cross. In the highest concentrations the result was negative, which means that the difference observed can be attributed, in part, to the high levels of P450, suggesting that increasing the metabolic capacity maximized the toxic effect of these doses. In the evaluation of carcinogenesis using the wts test, the results obtained for the same concentrations of UA show a positive result for the presence of tumors when compared to the negative control. We conclude that UA has recombinogenic, mutagenic and carcinogenic effects on somatic cells in D. melanogaster. 相似文献
25.
Lara Feulner Hamed S. Najafabadi Simon Tanguay Janusz Rak Yasser Riazalhosseini 《Urologic oncology》2019,37(2):166-175
Background
Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.Methods
Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.Results
Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.Conclusion
We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment. 相似文献26.
Kosuke Yoshihara Takayuki Enomoto Daisuke Aoki Yoh Watanabe Junzo Kigawa Nobuhiro Takeshima Hyoe Inomata Kana Hattori Masahisa Jinushi Hitoshi Tsuda Toru Sugiyama 《Cancer science》2020,111(9):3350-3358
Whether germline (g) breast cancer susceptibility gene (BRCA) mutations are located within or outside the ovarian cancer cluster region (OCCR) (1380‐4062 bp for gBRCA1, and between 3249‐5681 bp and 6645‐7471 bp for gBRCA2) may influence risk variations for ovarian cancers. This ad hoc analysis of the CHARLOTTE epidemiological study in Japan assessed the distribution of gBRCA1/2 mutations in patients with newly diagnosed ovarian cancer, and investigated an association between gBRCA1/2 mutation locations and ovarian cancer risk. Differences in patient background and clinical characteristics in subgroups stratified by gBRCA1/2 mutation locations were also evaluated. We analyzed the data of 93 patients (14.7%) from the CHARLOTTE study who were positive for gBRCA1/2 mutations. After excluding 16 cases with L63X founder mutation, 28 (65.1%) of gBRCA1 mutations were within the OCCR. Of 30 gBRCA2 mutations, 15 (50.0%) were within the OCCR. Of 27 patients (one patient excluded for unknown family history) with gBRCA1 mutations located in the OCCR, 11 (40.7%) had a family history of ovarian cancer; the proportion of patients with a family history of ovarian cancer and gBRCA1 mutations outside the OCCR was lower (13.3%). Sixty percent of patients with gBRCA1 mutations outside the OCCR had a family history of breast cancer; the proportion of patients with a family history of breast cancer and gBRCA1 mutations within the OCCR was relatively lower (33.3%). Understanding the mutation locations may contribute to more accurate risk assessments of susceptible individuals and early detection of ovarian cancer among gBRCA mutation carriers. 相似文献
27.
Shiyu Jiang Yan Qin Hongxin Jiang Biao Liu Jianming Shi Fanlu Meng Peng Liu Jianliang Yang Sheng Yang Xiaohui He Shengyu Zhou Lin Gui Hao Liu Jing Lin Han Han-Zhang Yuankai Shi 《International journal of cancer. Journal international du cancer》2020,147(9):2611-2620
Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients. 相似文献
28.
29.
30.
目的 分析m6A阅读器胰岛素样生长因子2-mRNA结合蛋白1(insulin-like growth factor 2 mRNA-binding protein 1,IGF2BP1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达水平及其对HCC患者预后的影响,并探讨IGF2BP1在HCC发生发展中的作用及其潜在机制。方法 基于5对HCC癌及相应癌旁组织mRNA-seq数据和TCGA数据库LIHC的mRNA-seq数据综合分析IGF2BP1在HCC中的表达情况,同时利用TCGA数据库中343例HCC患者的临床随访资料分析IGF2BP1表达水平对HCC患者总生存期的影响。基于TCGA数据库筛选IGF2BP1的共表达mRNA,并利用m6Avar在线网站预测mRNA的m6A位点及其RNA结合蛋白等信息,最终构建IGF2BP1的基因调控网络。结果 IGF2BP1基因在HCC中表达上调(log2FC HCC转录组数据=10.684,P<0.001;log2FC TCGA-LIHC数据集=7.032,P<0.001)。生存分析显示IGF2BP1低表达的HCC患者中位生存时间为5.84年,IGF2BP1高表达患者为4.44年,高表达患者总生存期缩短(P=0.011)。22个差异表达的mRNA与IGF2BP1存在靶向结合关系,并与其表达水平呈正相关。其中,HMGA2等15个高表达mRNA的HCC患者总生存期缩短。HMGA2、PEG10、CEP55、RHO、CDC6和KIF23基因中的潜在m6A甲基化位点位于mRNA 3'UTR端的miRNA结合区域。结论 IGF2BP1在HCC中高表达且导致患者总生存期缩短。IGF2BP1可能通过m6A甲基化及miRNA抑制作用的方式上调mRNA的表达,促进HCC发生并导致不良预后。 相似文献